Fungal infections are prevalent in several clinical settings, particularly in immunocompromised patients. The emergence of resistance to antimycotics, in particular to the azoles, has increased interest in therapeutic and prophylactic vaccination against these fungi [1]. Among fungal pathogens, Candida albicans is one of the most prevelent. This organism is one of the principal agents of widespread opportunistic infections in humans and causes candidiasis, a condition which is found in both normal and immunocompromised patients. There have been several attempts to provide anti-Candida vaccines.
Glucans are glucose-containing polysaccharides found inter alia in fungal cell walls. α-glucans include one or more α-linkages between glucose subunits and β-glucans include one or more β-linkages between glucose subunits. Within a typical fungal cell wall, β-1,3-glucan microfibrils are interwoven and crosslinked with chitin microfibrils to form the inner skeletal layer, whereas the outer layer consists of β-1,6-glucan and mannoproteins, linked to the inner layer via chitin and β-1,3-glucan.
In C. albicans, 50-70% of the cell wall is composed of β-1,3- and β-1,6-glucans. The use of β-glucans as anti-fungal vaccines is reviewed in reference 2. Protective antibodies against C. albicans β-1,6-glucan have been generated in mice [3,4]. Mice in which anti β-1,6-glucan antibodies were raised by vaccination with mannoprotein-depleted C. albicans cells were shown to have some protection against systemic challenge by C. albicans. Furthermore, mice passively immunised with these anti β-1,6-glucan antibodies demonstrated a raised level of protection against C. albicans. Similarly, anti-β-1,3-glucan antibodies have been found to be protective against C. albicans, and monoclonal antibodies that bind to β-1,3-glucans could protect against disseminated experimental cadidiasis [5].
It is an object of the invention to provide further and better glucan antigens for inducing protective and/or therapeutic immune responses against infections, particularly against fungal infections.